The goal of my study is to elucidate the molecular mechanisms by which lac repressor interacts with lac operator. The lactose operon of E. coli is chosen as a system in which the general principles of regulation of transcription can most easily be studied. Genetic methods will be used to isolate and characterize specific repressor mutants (a) with increased affinity for the operator, (b) which specifically overcome oc mutations, (c) which are defective in subunit aggregation. Operator mutants which increase the symmetry of the operator will also be selected, and the effect of these mutations on the repressor-operator interaction will be studied. A secondary binding site for the repressor will be mutated to increase its affinity for the repressor and make it function as an effective operator. My long-range concern is to identify the amino acid residues of the lac repressor and the base pairs of the lac operator which contribute to the repressor-operator interaction.